DNA. ncrna. Non-coding RNA analysis for gene expression regulation using bioinformatics tools

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1 non-coding RNA DNA RNA RNA non-coding RNA ncrna ncrna ncrna ncrna ncrna ncrna ncrna ncrna ncrna non-coding RNA Non-coding RNA analysis for gene expression regulation using bioinformatics tools Hayashi Chisato 1 Kwon Yeondae 2 Miyazaki Satoru 2 Abstract: Advances in genome analysis have revealed that a genomic DNA contains gene coding regions other than protein coding sequences and transcription-regulating regions. Among these regions, there exist RNA coding regions involved in transcription regulation as a primary function, RNAs transcribed from these regions are referred to as non-coding RNAs (ncrnas). ncrnas are known to affect regulation of transcription, but many functions are still unknown. On the other hand, since some ncrnas specifically express in a particular disease, they may have potential for being used as drug targets. Also, while most of ncrnas currently observed locate on intergenic regions of protein coding genes, some ncrnas locate on intronic regions of protein coding genes. The aim of this work is to predict ncrnas as drug targets regulating disease-associated genes based on positional relationship between protein genes and ncrnas on a genome. In this paper, we compare ncrnas located on intronic regions across species. Keywords: non-coding RNA, gene expression, intron, database 1. 1 Graduate School of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba , Japan 2 Department of Medical and Life Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science DNA RNA DNA c 2013 Information Processing Society of Japan 1

2 [1] RNA non-coding RNA ncrna ncrna [2], [3] ncrna ncrna small ncrna 200 ncrna long ncrna ncrna small ncrna RNA RNA interference: RNAi [4] RNAi ncrna mirna mrna [5] mirna [6], [7] mirna RNAi small ncrna long ncrna small ncrna long ncrna [8] long ncrna long ncrna [9], [10], [11] ncrna ncrna ncrna ncrna 2. ncrna mrna RNA snorna mrna snorna [12] ncrna [13] ncrna ncrna 1 2 ncrna Gene 3. intronic ncrna ncrna ncrna ncrna ncrna ncrna ncrna 3.1 ncrna ncrna H. sapiensm. musculusr. norvegicusd. melanogasters. cerevisiae C. elegans 6 Ensembl Genome [14] http: //asia.ensembl.orgindex.html ncrna Gene sets ncrna Transcript Sequence ncrna c 2013 Information Processing Society of Japan 2

3 1 ncrna intronic ncrna Organism ncrna intergenic intronic sense ncrna ncrna ncrna % H. sapiens 19,505 15,962 2, M.musculus 7,886 6,418 1, R. norvegicus 4,828 3, D. melanogaster 1,396 1, C. elegans 23,872 20,116 3, S. serevisiae intronic ncrna STATUS STSTUS H.sapiens M.musculus R.norvegicus D.melanogaster C.elegans S.cerevisiae mirna sense intronic sense over-lapping 13 2 misc RNA lincrna non coding/ncrna rrna snorna snrna trna prime over-lapping ncrna 18 2 ncrna host 2 pseudogene 415 Transcript locationncrna ncrna Gene 3 1 Gene Protein location Protein status ncrna Ensembl Gene sets protein coding ncrna ncrna 3 3 n 5 5 ( 1 ) intergenic ncrna ncrna n ncrna ncrna n+1 ( 2 ) intronic ncrna ncrna n ncrna ncrna 3 ncrna n+1 ( 3 ) sense ncrna ncrna ncrna ncrna 1 ncrna ncrna intronic ncrna 3.3 intronic ncrna STATUS 2 1 intronic ncrna STATUS 3.4 intronic ncrna intronic ncrna 2 ncrna RNAi mirna [5] intronic ncrna X c 2013 Information Processing Society of Japan 3

4 4 X mirna ENST ENSMUST 1 ncrna X intronic ncrna mirna ClustalX [15] 75 4 [16] 5 21 bl2seq [17] ncrna 1 ncrna RNAi ncrna intronic ncrna 2 ncrna mirna ncrna ncrna 4.2 intronic ncrna % ENST ENSMUST ENST ENST ENST ENSMUST ENST ENSMUST ENST ENST ENSMUST ENSMUST ENST ENST ENST ENST ENSMUST ENST ENSMUST ENSMUST ENST ENST ENST ENST ENSMUST ENST ENSMUST ENST ENST ENST ENST ENSMUST ENSMUST ENST ENSMUST ENST ENSMUST ENSMUST ENSMUST ENSMUST ENST ENST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENST ENSMUST ENST ENSMUST ENSMUST ENSMUST ENSMUST ENST ENSMUST ENST ENSMUST ENSMUST ENST ENSMUST ENSMUST ENSMUST ENSMUST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST X intronic mirna (Mean SD) 3 ncrna 5 mirna mirna node ncrna c 2013 Information Processing Society of Japan 4

5 3 21 % ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST ENST ENSMUST intronic ncrna 5. ncrna intronic ncrna ncrna ncrna ncrna ncrna ncrna intronic ncrna mirna 3.4 ncrna 6 lincrna long intergenic RNA [8] lincrna ncrna [1] Taft, R.J. and Mattick, J.S.: Increasing biological complexity is positively correlated with the relative genomewide expansion of non-protein-coding DNA sequences, Genome Biology, Vol.5, No.P1, pp.1 24 (2003). [2] Shiomi, H.: Non-coding RNAs as spatiotemporal regulators of genome network, Experimental Medicine, Vol.49, pp (2004). [3] Mattick, J.S.: RNA regulation: a new genetics?, Nature, Vol.5, pp (2004). [4] Fire, A., Xu, S., Montgomery, M.K., Kostas, S.A., Driver, S.E. and Mello, C.C.: Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans, Nature, Vol.391, pp (1997). [5] Krol, J., Loedige, I. and Filipowicz, W.: The widespread regulation of microrna biogenesis, function and decay, Nat Rev Genet, Vol.11, pp (2010). [6] Suzuki, H.I., Yamagata, K., Sugimoto, K., Iwamoto, T., Kato, S. and Miyazono, K.: Modulation of MicroRNA processing by p53, Nature, Vol.460, pp (2009). [7] Suzuki, H.I., Arase, M., Matsuyama, H., Choi, Y.L., Ueno, T., Mano, H., Sugimoto, K. and Miyazono, K.: MCPIP1 ribonuclease antagonizes Dicer and terminates microrna biogenesis through precursor microrna degradation, Molecular Cell, Vol.44, Issue 3, pp (2011). [8] Tsai, M.C., Spitale, R.C. and Chang, H.Y.: Long intergenic noncoding RNAs: New lincs in cancer progression, Cancer Res., Vo.71, pp.3 7 (2011). [9] Gibb, E.A., Brown, C.J. and Lam, W.L.: The functional role of long non-coding RNA in human carcinomas, Molecular Cancer, Vol.10, No.38, pp.1 17 (2011). [10] Mitra, S.A., Mitra, A.P. and Triche, T.J.: A central role for long non-coding RNA in cancer, Front Genet, Vol.3, Article 17, pp.1 9 (2012). [11] Liu, Q., Huang, J., Zhou, N., Zhang, Z., Zhang, A., Lu, Z., Wu, F. and Mo, Y.Y.: LncRNA loc is a p53-regulated tumor suppressor, Nucleic Acids Res., Vol.41, No.9, pp (2013). [12] Tycowski, K.T., Shu, M.D. and Steitz, J.A.: A mammalian gene with introns instead of exons generating stable RNA products, Nature, Vol.379, pp (1996). [13] Eleonora, C., Massone, S., Penna, I., Nizzari, M., Gigoni, A., Dieci, G., Russo, C., Florio, T., Cancedda, R. and Pagano, A.: An intronic ncrna-dependent regulation of SORL1 expression affecting A formation is upregulated in post-mortem Alzheimer s disease brain samples, Disease Model and Mechanisms, Vol.6, pp (2013). [14] Hubbard, T., Barker, D., Birney, E., Cameron, G., Chen, Y., et al.: The Ensembl Genome data project, c 2013 Information Processing Society of Japan 5

6 Nucleic Acids Res., Vol.30, pp (2002). [15] Larkin, M.A., Blackshields, G., Brown, N.P., Chenna, R., McGettigan, P.A., McWilliam, H., Valentin, F., Wallace, I.M., Wilm, A., Lopez, R., Thompson, J.D., Gibson, T.J. and Higgins, D.G.: Clustal W and Clustal X version 2.0, Bioinformatics, Vol.23, Issue 21, pp (2007). [16] Saitou, N. and Nei, M.: The neighbor-joining method: a new method for reconstructing phylogenetic trees, Molecular Biology and Evolution, Vol.4, No.4, pp (1987). [17] Tatusova, T.A. and Madden, T.L.: BLAST 2 Sequence, a new tool for comparing protein and nucleotide sequences, FEMS MICROBIOL LETT., Vol.174, No.2, pp (1999). c 2013 Information Processing Society of Japan 6